Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Toxicological evaluation of a propolis extract

La tintura de propóleos es un fitofármaco que tiene asociados diversos efectos farmacológicos: acción antimicrobiana, analgésica, antinflamatoria, antioxidante y cicatrizante. Según las normativas establecidas por la Organización para la Cooperación Económica y el Desarrollo (OECD), los ensayos toxicológicos constituyen un requerimiento para el registro de los fármacos, lo cual garantiza determinar un margen de seguridad para el uso de los productos que se evalúan. Para el estudio de toxicidad aguda oral se emplearon ratas Sprague-Dawley de ambos sexos, realizándose un ensayo límite donde se clasificó al extracto de propóleos en la categoría "sin clasificar", al ser administrado a una dosis de 2 g/Kg por vía oral en ratas. El estudio de irritabilidad dérmica se desarrolló en conejos albinos F1 machos, obteniéndose un índice de irritación primario igual a cero, con el cual se clasifica al producto como no irritante.The propolis extract is a phytomedicine. It is well know that propolis is associated with some pharmacological effects, as antimicrobian, analgesic, antinflammatory, antioxidant and healing actions. According to the normative setted dawn by OECD, toxicological assays are one of the requirements for drug registration, which guarantees the determination of a security margin for the use of the evaluated product. For acute toxicity studies, Sprague Dawley rats of both sexes were used in a limit assay carried out with propolis extract, on the basis of which was set into the unclassified category, when being administrated in one dose of 2 g/kg (p.o) in rats. The dermal irritability assay was carried out in albino rabbits F1. A primary irritation index equal to zero was obtained, which classifies the product as not irritating.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Toxicological evaluation of a propolis extract

La tintura de propóleos es un fitofármaco que tiene asociados diversos efectos farmacológicos: acción antimicrobiana, analgésica, antinflamatoria, antioxidante y cicatrizante. Según las normativas establecidas por la Organización para la Cooperación Económica y el Desarrollo (OECD), los ensayos toxicológicos constituyen un requerimiento para el registro de los fármacos, lo cual garantiza determinar un margen de seguridad para el uso de los productos que se evalúan. Para el estudio de toxicidad aguda oral se emplearon ratas Sprague-Dawley de ambos sexos, realizándose un ensayo límite donde se clasificó al extracto de propóleos en la categoría "sin clasificar", al ser administrado a una dosis de 2 g/Kg por vía oral en ratas. El estudio de irritabilidad dérmica se desarrolló en conejos albinos F1 machos, obteniéndose un índice de irritación primario igual a cero, con el cual se clasifica al producto como no irritante.The propolis extract is a phytomedicine. It is well know that propolis is associated with some pharmacological effects, as antimicrobian, analgesic, antinflammatory, antioxidant and healing actions. According to the normative setted dawn by OECD, toxicological assays are one of the requirements for drug registration, which guarantees the determination of a security margin for the use of the evaluated product. For acute toxicity studies, Sprague Dawley rats of both sexes were used in a limit assay carried out with propolis extract, on the basis of which was set into the unclassified category, when being administrated in one dose of 2 g/kg (p.o) in rats. The dermal irritability assay was carried out in albino rabbits F1. A primary irritation index equal to zero was obtained, which classifies the product as not irritating.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Oral acute toxicity assay of a phytomedicine elaborated with an extract of Musa paradisiaca pseudo-stem

El fitofármaco elaborado a partir del extracto de pseudotallo de Musa paradisiaca es un producto natural que presenta además en su composición miel de abejas (edulcorante) y propóleos (preservante). Entre los requisitos para el registro de medicamentos se encuentran los ensayos toxicológicos, los cuales garantizan un margen de seguridad para el empleo de los productos que son evaluados, según las normativas establecidas por la OECD. Para el estudio de toxicidad aguda oral se emplearon ratas Sprague- Dawley de ambos sexos, realizándose un ensayo límite donde se concluyó que el producto se clasifica en la categoría sin clasificar al ser administrado a una dosis única de 2000 mg/Kg por vía oral en ratas.The phytomedicine elaborated with a Musa paradisiaca pseudostalk extract is a natural product that also contains honeybee (edulcorant) and propolis (preservative). According to the normative setted down by OECD, toxicological assay is one of the requeriments for the drug registration which guarantees a security margin for the use of the evaluated product. For the study of acute oral toxicity, rats Sprague-Dawley of both sexes were used; a limit assay was carried out and the product was classified into unclassified category when being administrated in one dose of 2 g/Kg (p.o.) in rats.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Oral acute toxicity assay of a phytomedicine elaborated with an extract of Musa paradisiaca pseudo-stem

El fitofármaco elaborado a partir del extracto de pseudotallo de Musa paradisiaca es un producto natural que presenta además en su composición miel de abejas (edulcorante) y propóleos (preservante). Entre los requisitos para el registro de medicamentos se encuentran los ensayos toxicológicos, los cuales garantizan un margen de seguridad para el empleo de los productos que son evaluados, según las normativas establecidas por la OECD. Para el estudio de toxicidad aguda oral se emplearon ratas Sprague- Dawley de ambos sexos, realizándose un ensayo límite donde se concluyó que el producto se clasifica en la categoría sin clasificar al ser administrado a una dosis única de 2000 mg/Kg por vía oral en ratas.The phytomedicine elaborated with a Musa paradisiaca pseudostalk extract is a natural product that also contains honeybee (edulcorant) and propolis (preservative). According to the normative setted down by OECD, toxicological assay is one of the requeriments for the drug registration which guarantees a security margin for the use of the evaluated product. For the study of acute oral toxicity, rats Sprague-Dawley of both sexes were used; a limit assay was carried out and the product was classified into unclassified category when being administrated in one dose of 2 g/Kg (p.o.) in rats.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Oral acute toxicity assay of a phytomedicine elaborated with an extract of Musa paradisiaca pseudo-stem

El fitofármaco elaborado a partir del extracto de pseudotallo de Musa paradisiaca es un producto natural que presenta además en su composición miel de abejas (edulcorante) y propóleos (preservante). Entre los requisitos para el registro de medicamentos se encuentran los ensayos toxicológicos, los cuales garantizan un margen de seguridad para el empleo de los productos que son evaluados, según las normativas establecidas por la OECD. Para el estudio de toxicidad aguda oral se emplearon ratas Sprague- Dawley de ambos sexos, realizándose un ensayo límite donde se concluyó que el producto se clasifica en la categoría sin clasificar al ser administrado a una dosis única de 2000 mg/Kg por vía oral en ratas.The phytomedicine elaborated with a Musa paradisiaca pseudostalk extract is a natural product that also contains honeybee (edulcorant) and propolis (preservative). According to the normative setted down by OECD, toxicological assay is one of the requeriments for the drug registration which guarantees a security margin for the use of the evaluated product. For the study of acute oral toxicity, rats Sprague-Dawley of both sexes were used; a limit assay was carried out and the product was classified into unclassified category when being administrated in one dose of 2 g/Kg (p.o.) in rats.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Novel genes and sex differences in COVID-19 severity.

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided

Measurement of the production cross section of prompt Ξ0c baryons in p–Pb collisions at √sNN = 5.02 TeV

The transverse momentum (pT) differential production cross section of the promptly-produced charm-strange baryon Ξ0c (and its charge conjugate Ξ0c¯¯¯¯¯¯) is measured at midrapidity via its hadronic decay into π+Ξ− in p−Pb collisions at a centre-of-mass energy per nucleon−nucleon collision sNN−−−√ = 5.02 TeV with the ALICE detector at the LHC. The Ξ0c nuclear modification factor (RpPb), calculated from the cross sections in pp and p−Pb collisions, is presented and compared with the RpPb of Λ+c baryons. The ratios between the pT-differential production cross section of Ξ0c baryons and those of D0 mesons and Λ+c baryons are also reported and compared with results at forward and backward rapidity from the LHCb Collaboration. The measurements of the production cross section of prompt Ξ0c baryons are compared with a model based on perturbative QCD calculations of charm-quark production cross sections, which includes only cold nuclear matter effects in p−Pb collisions, and underestimates the measurement by a factor of about 50. This discrepancy is reduced when the data is compared with a model in which hadronisation is implemented via quark coalescence. The pT-integrated cross section of prompt Ξ0c-baryon production at midrapidity extrapolated down to pT = 0 is also reported. These measurements offer insights and constraints for theoretical calculations of the hadronisation process. Additionally, they provide inputs for the calculation of the charm production cross section in p−Pb collisions at midrapidity

Measurement of Ω0c baryon production and branching-fraction ratio BR(Ω0c → Ω−e+νe)/BR(Ω0c → Ω−π+) in pp collisions at √s = 13 TeV

The inclusive production of the charm-strange baryon Ω0c is measured for the first time via its semileptonic decay into Ω−e+νe at midrapidity (|y| < 0.8) in proton–proton (pp) collisions at the centre-of-mass energy √s = 13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 < pT < 12 GeV/c. The branching-fraction ratio BR(Ω0c → Ω−e+νe)/BR(Ω0c → Ω−π+) is measured to be 1.12 ± 0.22 (stat.) ± 0.27 (syst.). Comparisons with other experimental measurements, as well as with theoretical calculations, are presented

Measurement of the impact-parameter dependent azimuthal anisotropy in coherent ρ0 photoproduction in Pb–Pb collisions at √sNN = 5.02 TeV

The first measurement of the impact-parameter dependent angular anisotropy in the decay of coherently photoproduced ρ0 mesons is presented. The ρ0 mesons are reconstructed through their decay into a pion pair. The measured anisotropy corresponds to the amplitude of the cos(2ϕ) modulation, where ϕ is the angle between the two vectors formed by the sum and the difference of the transverse momenta of the pions, respectively. The measurement was performed by the ALICE Collaboration at the LHC using data from ultraperipheral Pb−Pb collisions at a center-of-mass energy of sNN−−−√ = 5.02 TeV per nucleon pair. Different impact-parameter regions are selected by classifying the events in nuclear-breakup classes. The amplitude of the cos(2ϕ) modulation is found to increase by about one order of magnitude from large to small impact parameters. Theoretical calculations, which describe the measurement, explain the cos(2ϕ) anisotropy as the result of a quantum interference effect at the femtometer scale that arises from the ambiguity as to which of the nuclei is the source of the photon in the interaction